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Biomedical subjects

K Miwa

Publications and source records attributed to K Miwa.

At least 127 records · Page 7Linked to original sources
PubMed1999

[A new exanthematous disease in newborn infants caused by exotoxins producing Staphylococcus aureus; exotoxins production of the isolates and serum levels of antitoxin antibody in the patients and umbilical cord blood].

Recently, in Japan newly neonatal exanthematous disease was elucidated to be caused by staphyloccocal supcrantigcnic exotoxins, mainly TSST-1. We studied exotoxins producibility of 43 strains of S. aureus isolated from neonates with exanthematous disease and examined antibody titers to staphylococcal enterotoxin A, B, C (SEA, SEB, SEC) and toxic shock syndrome toxin 1 (TSST-1) of the patients and control (umbilical cord blood from term infants). The results were as follows 1.34 of 43 strains (79%) isolated from the patients were SEC and TSST-1 producing MRSA, 5 strains (12%) were SEB, SEC, and TSST-1 producing MRSA, 1 strain (2%) was SEB and TSST-1 producing MRSA, 2 strains (12%) were SEB producing MSSA and did not produce TSST-1. The 1 strain (2%) was MSSA which produced SEC and TSST-1. 2. 16 neonates with exanthematous disease, who showed typical clinical signs and laboratry findings of thrombocytopenia, with SEC and TSST-1 producing MRSA isolates had significantly low anti-TSST-1 antibody titers at onset (p < 0.05), compared with the control (umbilical cord blood from term infants): TSST-1 appeared to the causative agent for the disease. In two neonates with exanthematous disease, with SEB- and non- TSST-1-producing MSSA isolates, anti-SEB antibody titers were low at onset, so SEB appeared to the causative agent for the disease. 3. In Japan, low anti-TSST-1 antibody titers were found in the umbilical blood samples from about 70% of term infants; and low anti-SEB or anti-SEC antibody titers were found in samples from only about 10% of them, that is, a number of term infants had anti-SEB and anti-SEC antibodies. The majority of S. aureus isolated from neonates with exanthematous disease were enterotoxin- and TSST-1-producing MRSAs. The results of our study by measuring antitoxin antibody titers suggested that SEB and SEC might not be pathogenically responsible, but TSST-1 was considered to be responsible for the majority of exanthematous disease. Prevalence of TSST-1-producing MRSA in the neonatal and premature baby ward is the main cause for the high incidence of this disease in Japan, whereas the low antibody titer to TSST-1 in the mother, in comparison with the anti-enterotoxin antibody titers, may also be a predisposing factor.

Antibodies, Bacterial↗
PubMed1999

A protein kinase C-beta-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats.

Increased protein kinase C (PKC) activity has been implicated in the pathogenesis of diabetic retinopathy and nephropathy. However, the role of PKC in diabetic neuropathy remains unclear. The present study was conducted to compare the effect of PKC inhibition by a PKC-beta-selective inhibitor, LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ). Streptozotocin-induced diabetic rats were treated with or without LY and/or NZ for 4 weeks, and motor nerve conduction velocity (MNCV), coefficient of variation of R-R interval (CVR-R), sciatic nerve blood flow (SNBF), peak latencies of oscillatory potentials on electroretinogram, PKC activities in membranous and cytosolic fractions of sciatic nerves, and polyol contents in the tail nerves were measured. Untreated diabetic rats demonstrated delayed MNCV, decreased CVR-R, reduced SNBF, and prolonged peak latencies of oscillatory potentials. Treatment with LY as well as NZ prevented all these deficits in diabetic rats. There were no significant differences in PKC activities in membranous or cytosolic fractions of sciatic nerves between normal and diabetic rats. Treatment with neither LY nor NZ altered PKC activities. Nerve myo-inositol depletion in diabetic rats was ameliorated not only by NZ, but also by LY. These observations suggest that inhibition of PKC-beta by LY may have a beneficial effect in preventing the development of diabetic nerve dysfunction, and that this effect may be mediated through its action on the endoneurial micro-vasculature.

Aldehyde Reductase↗
PubMed1999

Activated lansoprazole inhibits cancer cell adhesion to extracellular matrix components.

Integrins play an important role in tumor dissemination. The purpose of this study was to examine whether a SH-reactive reagent inhibits the adhesion of the human pancreatic cancer cell line AsPC-1 to extracellular matrix components. Activated lansoprazole (AG-2000) was used as the SH-reactive reagent because this compound is known to react with SH groups but does not permeate the cell membrane. The effect of AG-2000 on the adhesion of AsPC-1 cells to matrix was examined, using both an in vitro adhesion assay and an in vivo nude mouse xenograft model of peritoneal implantation. In the in vitro adhesion assay, a 60-min exposure of AsPC-1 cells to AG-2000 resulted in a dose-dependent inhibition of AsPC-1 cell adhesion to laminin, fibronectin and type IV collagen, although AG-2000 did not affect the viability of AsPC-1 cells by MTT assay. In the in vivo assessment of AsPC-1 cell implantation, the AsPC-1 cells were initially preincubated with AG-2000 for 60 min to ensure adequate exposure of the AsPC-1 cells to AG-2000 before intraperitoneal injection. AG-2000 significantly inhibited the peritoneal implantation of the AsPC-1 cells in nude mice. These findings suggest that a short exposure of cancer cells to AG-2000 can inhibit cancer cell adhesion to extracellular matrix components.

Animals↗
PubMed1999

Effect of its demethylated metabolite on the pharmacokinetics of unchanged TAK-603, a new antirheumatic agent, in rats.

A factor in the dose-dependent pharmacokinetics of ethyl 4-(3, 4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2, 4-triazol-1-yl-methyl)quinoline-3-carboxylate (TAK-603) in rats was shown to be due to the inhibition of metabolic clearance of unchanged TAK-603 by its major metabolite, M-I, in other words, product inhibition. The effect of M-I on the metabolic clearance of TAK-603 was studied using rats continuously infused i.v. with this metabolite at rates of 5.3 and 16.0 mg/h/kg. The total body clearance of TAK-603 was decreased remarkably in M-I-infused rats, and the decline of total body clearance depended on the steady-state plasma concentrations of M-I. The effect of M-I generated from the dosed parent drug on the plasma concentration-time profile of TAK-603 was investigated using bile-cannulated rats after i.v. injection of 14C-labeled TAK-603 at doses of 1 and 15 mg/kg. Elimination rates of TAK-603 from rat plasma increased in the bile-cannulated rats in which systemic M-I levels were reduced by interrupting its enterohepatic circulation. To express, simultaneously, the relationships between TAK-603 and M-I in plasma concentration-time profiles, a kinetic model based on the product inhibition was developed for the bile-cannulated rats. A good agreement between calculated curves and the observed concentrations of both TAK-603 and M-I was found at 1 and 15 mg/kg, and the calculated curves were drawn using constant parameters for the two dosages. These results show that the product inhibition by M-I is one factor responsible for the dose-dependent pharmacokinetics of TAK-603 in rats.

Animals↗
PubMed1999

[A case report: modified PMUE therapy might be effective for advanced gastric carcinoma with pulmonary carcinomatous lymphangitis].

A regimen featuring a combination of CDDP, MMC, 5-FU and ETP (Modified-PMUE) was given to a patient with advanced gastric cancer containing pulmonary carcinomatous lymphangitis. This procedure made his carcinomatous lymphangitis disappear and primary and metastatic lesions reduce in size. The subsequent palliative reduction surgery for gastric carcinoma, proximal gastrectomy was feasible. Nevertheless, postoperative Modified-PMUE was ineffective: carcinomatous lymphangitis reappeared and progressed to death of respiratory failure postoperative 68 days. The SDI test, a sensitivity test for carcinostatic agent showed neither CDDP, MMC, 5-FU nor ETP sensitive to resected carcinoma cells. Therefore, we concluded that the Modified PMUE kills carcinoma cells sensitive to the agents and allows carcinoma cells resistant to the agents to grow.

Adenocarcinoma↗
PubMed1999

[Study of transforming growth factor-alpha expression in duodenal ulcer].

Various growth factors were also reported to promote healing of peptic ulcer. We have used a monoclonal antibody in conjunction with a standard immunohistochemical technique to characterize the expression of transforming growth factor-alpha (TGF-alpha) in duodenal ulcer. TGF-alpha immunoreactivity is found in Brunner's gland, also in immature gland and in duodenal epitheliums, but not in gastric metaplasia of the duodenum. TGF-alpha expression of healing and scar stage was higher than that of active stage. The presence or absence of Helicobacter pylori infection did not affect the expression of TGF-alpha in duodenal ulcer.

Adult↗
PubMed1999

Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer.

Neogenesis of lymphatic vessel and lymphatic invasion is frequently found in the stroma of cancers, but the mechanisms of this phenomenon remain unclear. Vascular endothelial growth factor C (VEGF-C) is known to be the only growth factor for the lymphatic vascular system, and its receptor has been identified as Flt4. To clarify the mechanism of lymphatic invasion in cancer, we studied the expression of VEGF-C and flt4 genes in gastric cancer tissues. VEGF-C mRNA was mainly expressed in primary tumors (15 of 32; 47%), but the frequency of VEGF-C mRNA expression was low in normal mucosa (4 of 32; 13%). In primary tumors, there was a significant relationship between VEGF-C and flt4 mRNA expression. In contrast, Flt4 was mainly expressed on the lymphatic endothelial cells but not in cancer cells. A strong correlation was found between VEGF-C expression and lymph node status, lymphatic invasion, venous invasion, and tumor infiltrating patterns. Cancer cells in the lymphatic vessels frequently showed intracytoplasmic VEGF-C immunoreactivity. Furthermore, there was a close correlation between VEGF-C tissue status and the grade of lymph node metastasis. Patients with high expression of VEGF-C protein had a significantly poorer prognosis than did those in low VEGF-C expression group. By the Cox regression model, depth of wall invasion, lymph node metastasis, and VEGF-C tissue status emerged as independent prognostic parameters, and the VEGF-C tissue status was ranked third as an independent risk factor for death. These results strongly suggest that cancer cells producing VEGF-C may induce the proliferation and dilation of lymphatic vessels, resulting in the development of invasion of cancer cells into the lymphatic vessel and lymph node metastasis.

Biomarkers, Tumor↗
PubMed1999

[Surgery for metastatic brain and spinal tumor from colorectal cancer].

UNLABELLED: The results of invasive treatment of brain metastasis of colorectal cancer (6 cases) and spinal metastasis of colorectal cancer (3 cases), aimed at alleviating the symptoms, were analyzed. In all 6 cases of brain metastasis, metastases were also found in some other remote sites (often the liver). The average period from resection of the primary lesion to resection of the brain metastasis was 3 years and 3 months for this group. Of these 6 cases, 5 had cerebral metastasis and 1 had cerebellar metastasis. The preoperative performance status (PS) was 1 in 1 case and 2 in 5 cases. After surgery, the PS improved in all 6 cases, allowing all the patients to be discharged. There was only one patient whose death was attributable to brain metastasis. In all 3 cases of spinal metastasis, metastases were also detected in the lungs or liver (synchronous in) 1 case, metachronous in 2 cases). The preoperative PS was 2 in 1 case, 3 in 1 case and 4 in 1 case. After surgery, the PS improved in 2 cases. One of the three patients is still alive. CONCLUSION: The results of this study suggest that it is not impossible to improve the QOL of patients with brain or spinal metastasis of cancer by surgical intervention, although the response may vary from patient to patient.

Brain Neoplasms↗
PubMed1998

Dye-Guided Sentinel Lymphadenectomy in Clinically Node-Negative and Node-Positive Breast Cancer Patients.

BACKGROUND: Sentinel lymphadenectomy has been used to assess the axillary nodal status in patients with breast cancer in an attempt to avoid unnecessary axillary dissection. Most studies have examined the utility of this procedure in clinically node-negative patients. However, the clinical evaluation of axillary nodes is often inaccurate for both clinically node-negative and clinically node-positive patients. METHODS: We performed dye-guided sentinel lymphadenectomy in both clinically node-negative and clinically node-positive patients with breast cancer. All patients also underwent a formal axillary dissection. The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) werecompared with each other and with histologic findings of the nonsentinel nodes. RESULTS: The SLN was identified in 30 (79%) of 38 patients with clinically negative nodes, and in 11 (92%) of 12 patients with clinically positive nodes. Forclinically node-negative patients, SLN evaluation yielded a diagnostic accuracyof 90%, a sensitivitiy of 72%, and a specificity of 100%. For clinically node-positive patients, these values were 100%, 100% and 100%, respectively. These values were not significantly different for the two groups of patients. CONCLUSION: Sentinel lymphadenectomy may be useful in assessing the axillarynodal status of both clinically node-positive and clinically node-negative breast cancer patients.

Journal Article↗
PubMed1998

Expanding the Role of Breast-Cancerving Therapy Using Immediate Volume Replacement.

Preventing local recurrence and preserving cosmetic appearance are often in conflict in breast-conserving therapy. Immediate volume replacement with autogenous tissue has been developed to allow a wider excision without compromising the aesthetic results. A review of the literature regarding immediate volume replacement in breast-conserving therapy has led to the following conclusions. When excision of the skin overlying the tumor is unnecessary, a transverse or lateral incision should be used which allows wide excision and immediate volume replacement with autogenous tissue while minimizing scar morbidity. The options for immediate volume replacement include the latissimus dorsi flap with adipose tissue, the latissimus dorsi myocutaneous flap, and the lateral thoracic adipose tissue flap. The choice of technique depends on the amount and position of the skin, subcutaneous tissue, and breast tissue which must be excised. These procedures can be used to extend the indications for breast-conserving therapy, eliminating the need for mastectomy in selected patients. Future developments in the endoscopic harvesting of flaps may further expand the role of volume replacement.

Journal Article↗
PubMed1998

Sentinel Lymphadenectomy in Breast Cancer: An Alternative to Routine Axillary Dissection.

We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of lymphoscintigraphy and dye-guided and/or gamma probe-guided techniques are superior to either technique alone for identifying the sentinel lymph node. (b) lmmediate and reliable intraoperative information on the sentinel node is vital for the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot be identified. (c) A reverse transcriptase-polymerase chain reaction(RT-PCR)method is more sensitive than immunohistochemistry for the detection of micrometastasis in the sentinel node. (d) Until there are new tumor markers or new imaging techniques to identify axillary metastasis without operative intervention, sentinel lymphadenectomy is a highly accurate, minimally invasive way to assess disease extent. Before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer, however, a large clinical trial will be essential to verify the value of this technology.

Journal Article↗
PubMed1998

The Role of Hormonal Therapy in Breast Cancer.

This review reassesses the role of hormonal therapy in breast cancer specifically the sequential or concurrent use of endocrine therapy and the combined use of chemotherapy with endocrine therapy. In advanced disease the sequential use of hormone therapies is generally recommended rather than the combined use of various hormonal agents, though combination hormonal therapy offers advantages in certain subsets of patients. The efficacy of combined chemo-endocrine therapy is questionable. Chemotherapy with estrogenic recruitment is an attractive but still experimental concept. However, in an adjuvant setting there is evidence that combined chemo-endocrine therapy causes a significant increase in disease-free and/or overall survival, particularly in postmenopausal patients with estrogen receptor(ER)-positive tumors. While hormonal treatment strategies have clearly benefitted from randomized studies, data regarding optimal endocrine therapy are still insufficient.

Journal Article↗
PubMed1998

The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor.

BACKGROUND: Hepatocyte growth factor receptor (c-met), autocrine motility factor receptor (AMFR), and urokinase-type plasminogen activator receptor (uPAR) are known to play important roles in tumor cell migration, invasion, and metastasis. The authors studied the relation between the expression patterns of these genes and the growth patterns of human gastric carcinoma. METHODS: The relation between the expression of c-met, AMFR, and uPAR and clinicopathologic parameters was studied using immunohistochemical preparations from 102 paraffin embedded primary gastric carcinomas. RESULTS: Of 102 cases, 43 (42%) had overexpression of c-met, and AMFR and uPAR immunoreactivity was observed in 41 cases (40%) and 38 cases (37%), respectively. Macroscopic examination revealed that all three genes were expressed in 1 (3%) of 32 early stage gastric carcinomas, 0 (0%) of 29 localized carcinomas (Borrmann types 1 and 2), and 16 (39%) of 41 infiltrating carcinomas (Borrmann types 3 and 4). In particular, the incidence (68%, 13 of 19 cases) of simultaneous expression of the three genes was significantly higher in Borrmann type 4 gastric carcinoma than in the other macroscopic types (P < 0.01). The overexpression of these genes was also closely associated with lymph node metastasis and peritoneal dissemination. In addition, the simultaneous overexpression of the three genes was associated with positive lymphatic vessel invasion and infiltrating type. Patients with tumors that simultaneously expressed all three genes had significantly poorer prognoses than those with tumors expressing only one or two of the genes. Furthermore, the number of genes expressed was closely related to the prognosis, and the Cox proportional hazards model identified this as one of the independent prognostic factors. CONCLUSIONS: These results suggest that the expression patterns of c-met, AMFR, and uPAR may be closely associated with the progression and invasion of gastric carcinoma as well as the prognoses of the patients. Borrmann type 4 gastric carcinoma is characterized by the diverse and simultaneous expression of these three genes.

Adult↗
PubMed1998

The Role of Internal Mammary Lymph Node Metastases in the Management of Breast Cancer.

We reviewed the literature regarding internal mammary lymph node metastasis in the management of breast cancer. Internal mammary dissection or radiotherapy provides no survival advantage in breast cancer patients. However, internal mammary nodal metastasis is an important independent prognostic factor. Patients with such metastases are candidates for systemic adjuvant hormonal therapy and/or chemotherapy. Moreover, in patients with histologically confirmed internal mammary metastases, irradiation of the nodes is appropriate for local control. Noninvasive techniques, such as internal mammary lymphoscintigraphy, parasternal sonography, computed tomography, and magnetic resonance imaging, are not satisfactory for the practical diagnosis of internal mammary metastasis. At present, biopsy of the internal mammary nodes in the first and second intercostal spaces is indicated for assessing nodal status and planning treatment.

Journal Article↗
PubMed1998

Transgenic expression of Fas in T cells blocks lymphoproliferation but not autoimmune disease in MRL-lpr mice.

Fas is a member of the TNF receptor family. Binding of Fas ligand to Fas induces apoptosis in Fas-bearing cells. Fas is expressed in various cells, including thymocytes, peripheral T cells, and activated B cells. The mouse lpr mutation is a loss of function mutation of Fas. MRL-lpr/lpr mice develop lymphadenopathy and splenomegaly, and produce multiple autoantibodies, which results in autoimmune disease. In this report, we describe the establishment of a line of Fas transgenic MRL-lpr mice in which mouse Fas cDNA was expressed using the T cell-specific murine lck promoter. The transgenic mice expressed functional Fas in thymocytes and peripheral T cells, but not in B cells. The transgenic mice did not accumulate abnormal T cells (Thy-1+ B220+), but still accumulated B cells (Thy-1- B220+); they produced a large quantity of Igs (IgG1 and IgG2a), including anti-DNA Abs, and developed glomerulonephritis. These results suggest that autoreactive or activated B cells must be killed through Fas expressed in the B cells by the Fas ligand expressed in activated T cells.

Animals↗
PubMed1998

Therapeutic strategies and long-term results in differentiated thyroid cancer.

Differentiated thyroid carcinoma (DTC) is usually an indolent tumor associated with a low mortality. However, DTC, particularly papillary thyroid carcinoma, happens to be a multicentric tumor and tends to spread to the regional lymph nodes in the early stage of the disease; some patients with DTC do die from metastatic or recurrent disease. Despite the small number of these patients, therapeutic strategies designed to prevent such outcomes should be pursued. In this review, we attempt to evaluate the impact of different therapeutic strategies on survival and recurrence. Consequently, we conclude that the surgical approach to DIC should be individualized on the basis of the biologic behavior of the tumor, rather than on the extent of cancer involvement in the thyroid and regional lymph nodes. It is mandatory to expand our efforts to identify high-risk patients more accurately, thereby facilitating more rational approaches to treatment.

Combined Modality Therapy↗